Optimised procurement of cancer-reactive T-cell receptors from clinical samples

Caillaud, Marine E., Rius, Cristina, Morin, Théo, Tan, Li Rong, Thomas, Hannah L., Rogers, Amber, Hick, Joshua, Nielsen, Morten, Hasan, Md Samiul, Svane, Inge Marie, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 and Dolton, Garry 2026. Optimised procurement of cancer-reactive T-cell receptors from clinical samples. Immunotherapy Advances 6 (1) , ltag009. 10.1093/immadv/ltag009

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Introduction T-cell receptors can sense cancer-associated changes in cellular proteins, lipids, metabolites, and stress pathways, enabling immune-mediated tumour elimination in some patients. These receptors underpin T-cell receptor-based immunotherapies, yet their isolation from clinical samples remains challenging due to labour-intensive workflows, dependence on prior antigen knowledge, and loss of cell viability. Methods We developed an optimised flow cytometry-based assay, termed the T107 assay, to isolate viable cancer-reactive T-cells directly from clinical samples. Following short-term exposure to cancer cells, responding T-cells are identified by simultaneous surface detection of tumour necrosis factor and the degranulation marker CD107a, enabling recovery of live antigen-reactive cells for downstream analysis. Results The T107 assay enabled rapid identification of cancer-reactive T-cells from tumour-infiltrating lymphocyte products derived from melanoma and sarcoma patients. The assay supported phenotypic and functional characterisation of αβ and γδ T-cell receptor populations, including CD4+ and CD8+ subsets, responding to both patient-specific and shared cancer antigens. Isolation of viable responding cells enabled high-resolution receptor sequencing, generation of functional T-cell clones, determination of antigen specificity and major histocompatibility complex restriction or independence. Paired receptors were engineered into primary T-cells to generate T-cell receptor-engineered products capable of recognising multiple cancer types. Conclusions The T107 assay provides a rapid and robust method for antigen-agnostic procurement of viable cancer-reactive T-cells and their receptors from clinical material. This approach removes key bottlenecks in T-cell receptor discovery and is expected to accelerate development of T-cell receptor-based immunotherapies across a broad range of cancers.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2026-06-22
Publisher:	Oxford University Press
Funders:	Wellcome Trust
Projects:	220295/Z/20/Z
Date of First Compliant Deposit:	6 July 2026
Date of Acceptance:	11 May 2026
Last Modified:	03 Sep 2026 11:49
URI:	https://orca.cardiff.ac.uk/id/eprint/187970

Actions (repository staff only)

Edit Item